Transplantation of SNAP-treated adipose tissue-derived stem cells improves cardiac function and induces neovascularization after myocardium infarct in rats

Exp Mol Pathol. 2011 Apr;90(2):149-56. doi: 10.1016/j.yexmp.2010.11.005. Epub 2010 Nov 25.

Abstract

Stem cell therapy has been considered a promise for damaged myocardial tissue. We have previously shown that S-nitroso-N-acetyl-D,L-penicillamine (SNAP) increases the expression of several muscular markers and VEGF in mesenchymal stem cells, indicating that transplantation of SNAP-treated cells could provide better functional outcomes. Here, we transplanted SNAP-treated adipose tissue-derived stem cells (ADSCs) in rat infarcted myocardium. After 30days, we observed a significant improvement of the ejection fraction in rats that received SNAP-treated ADSCs, compared with those that received untreated cells (p=0.008). Immunohistochemical reactions showed an increased expression of troponin T-C and von Willebrand factor, and organized vascular units in the infarcted area of tissue transplanted with treated ADSCs. SNAP exposure induced intracellular S-nitrosation, a decreased GSH/GSSG ratio, but did not increase cGMP levels. Collectively, these results indicate that SNAP alters the redox environment of ADSCs, possibly associated with a pre-differentiation state, which may improve cardiac function after transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Glutathione / metabolism
  • Green Fluorescent Proteins / metabolism
  • Heart / drug effects
  • Heart / physiopathology*
  • Heart Function Tests / drug effects
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Male
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Neovascularization, Physiologic / drug effects*
  • Nitrosation / drug effects
  • Rats
  • Rats, Wistar
  • S-Nitroso-N-Acetylpenicillamine / pharmacology*
  • Stem Cell Transplantation*
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Stroke Volume / drug effects
  • Troponin / metabolism
  • von Willebrand Factor / metabolism

Substances

  • Troponin
  • von Willebrand Factor
  • Green Fluorescent Proteins
  • S-Nitroso-N-Acetylpenicillamine
  • Glutathione